Knockdown of Human Oxa1l Impairs the Biogenesis of F1Fo-ATP Synthase and NADH:Ubiquinone Oxidoreductase

Stibůrek, Lukáš; Fornůsková, Daniela; Wenchich, László; Pejznochova, Martina; Hansı́ková, Hana; Zeman, Jiřı́

doi:10.1016/j.jmb.2007.09.044

Cited by 80 publications

(79 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Acid tolerance in S. mutans is mediated in part by the F 1 F -ATPase that hydrolyses ATP to pump protons across the plasma membrane into the extracellular space. YidC and Oxa1 are known to play crucial roles in assembly of the F 1 F -ATPase complex (6,8,10,11). In S. mutans, elimination of YidC2 or signal recognition particle components have comparable negative effects on membrane associated ATPase activity (20).…”

Section: Rattus Norvegicus R a Tt U S N O Rv Eg Ic U S Mus Musculus Mmentioning

confidence: 99%

“…Oxa1 plays an essential role during diverse steps of inner membrane biogenesis, in particular during the membrane insertion of mitochondrial translation products, the assembly of cytochrome oxidase, and of the membrane sector of the F 1 F o -ATPase (8)(9)(10)(11). In addition to Oxa1, mitochondria contain a second member of the YidC/Oxa/ Alb3 family named Cox18 or Oxa2 (12)(13)(14).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Independent gene duplications of the YidC/Oxa/Alb3 family enabled a specialized cotranslational function

Funes¹,

Hasona

Bauerschmitt³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

YidC/Oxa/Alb3 family proteins catalyze the insertion of integral membrane proteins in bacteria, mitochondria, and chloroplasts, respectively. Unlike gram-negative organisms, gram-positive bacteria express 2 paralogs of this family, YidC1/SpoIIIJ and YidC2/ YgjG. In Streptococcus mutans, deletion of yidC2 results in a stress-sensitive phenotype similar to that of mutants lacking the signal recognition particle (SRP) protein translocation pathway, while deletion of yidC1 has a less severe phenotype. In contrast to eukaryotes and gram-negative bacteria, SRP-deficient mutants are viable in S. mutans; however, double SRP-yidC2 mutants are severely compromised. Thus, YidC2 may enable loss of the SRP by playing an independent but overlapping role in cotranslational protein insertion into the membrane. This is reminiscent of the situation in mitochondria that lack an SRP pathway and where Oxa1 facilitates cotranslational membrane protein insertion by binding directly to translation-active ribosomes. Here, we show that OXA1 complements a lack of yidC2 in S. mutans. YidC2 also functions reciprocally in oxa1-deficient Saccharomyces cerevisiae mutants and mediates the cotranslational insertion of mitochondrial translation products into the inner membrane. YidC2, like Oxa1, contains a positively charged C-terminal extension and associates with translating ribosomes. Our results are consistent with a gene-duplication event in gram-positive bacteria that enabled the specialization of a YidC isoform that mediates cotranslational activity independent of an SRP pathway. membrane protein insertion ͉ mitochondria ͉ Streptococcus mutans ͉ gram-positive bacteria ͉ ribosomes

show abstract

Section: Rattus Norvegicus R a Tt U S N O Rv Eg Ic U S Mus Musculus Mmentioning

confidence: 99%

mentioning

confidence: 99%

Independent gene duplications of the YidC/Oxa/Alb3 family enabled a specialized cotranslational function

Funes¹,

Hasona

Bauerschmitt³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…OXA1L gene encodes a mitochondrial integral membrane protein required for the correct biogenesis of F(1)F(o)-ATP synthase and NADH:ubiquinone oxidoreductase. 28 Considering that the homozygote patient with DelE6-E11 (patient no. 5) has a severe but characteristic LPI phenotype, the deletion of this sequence from the OXA1L 5 0 region may not affect the transcription of this contiguous gene, but further enzymatic deficiency studies of the OXPHOS system should be performed in this patient to confirm this.…”

Section: Slc7a7mentioning

confidence: 99%

Novel SLC7A7 large rearrangements in lysinuric protein intolerance patients involving the same AluY repeat

et al. 2008

View full text Add to dashboard Cite

Lysinuric protein intolerance (LPI) is a rare autosomal inherited disease caused by defective cationic aminoacid transport 4F2hc/y þ LAT-1 at the basolateral membrane of epithelial cells in the intestine and kidney. LPI is a multisystemic disease with a variety of clinical symptoms such as hepatosplenomegaly, osteoporosis, hypotonia, developmental delay, pulmonary insufficiency or end-stage renal disease. The SLC7A7 gene, which encodes the y þ LAT-1 protein, is mutated in LPI patients. Mutation analysis of the promoter localized in intron 1 and all exons of the SLC7A7 gene was performed in 11 patients from 9 unrelated LPI families. Point mutation screening was performed by exon direct sequencing and a new multiplex ligation probe amplification (MLPA) assay was set up for large rearrangement analysis. Eleven SLC7A7-specific mutations were identified, seven of them were novel: p.L124P, p.C425R, p.R468X, p.Y274fsX21, c.625 þ 1G4C, DelE4-E11 and DelE6-E11. The novel large deletions originated by the recombination of Alu repeats at introns 3 and 5, respectively, with the same AluY sequence localized at the SLC7A7 3 0 region. The novel MLPA assay is robust and valuable for LPI molecular diagnosis. Our results suggest that genomic rearrangements of SLC7A7 play a more important role in LPI than has been reported, increasing the detection rate from 5.1 to 21.4%. Moreover, the 3 0 region AluY repeat could be a recombination hot spot as it is involved in 38% of all SLC7A7 rearranged chromosomes described so far.

show abstract

“…The human homolog of Oxa1, OXA1L, also physically interacts with mitochondrial ribosomes via its C-terminal tail (41,42) and is able to restore COX assembly in an OXA1 null yeast strain, arguing that Oxa1-dependent insertion of the N-terminal transmembrane domain of Cox2 and the simultaneous translocation of its N-terminus into the IMS is an evolutionarily conserved function (43) ( Figure 1B). However, OXA1L knockdown in HEK293 cells leads to a diminution in the abundance of Complexes I and V rather than COX (44). This has led to the suggestion that in mammals COX20 may be sufficient for insertion of the N-terminal transmembrane domain of COX2, given that its hydrophilic N-terminus is shorter than that of yeast Cox2 and does not require proteolytic processing upon membrane insertion (45).…”

Section: The Translocation Of Its N-terminus Into the Imsmentioning

confidence: 99%

Building the CuA site of cytochrome c oxidase: A complicated, redox-dependent process driven by a surprisingly large complement of accessory proteins

Jett

Leary

2018

Journal of Biological Chemistry

View full text Add to dashboard Cite

Cytochrome c oxidase (COX) was initially purified more than 70 years ago. A tremendous amount of insight into its structure and function has since been gleaned from biochemical, biophysical, genetic and molecular studies. As a result, we now appreciate that COX relies on its redox-active metal centers (heme a and a 3 , Cu A and Cu B ) to reduce oxygen and pump protons in a reaction essential for most eukaryotic life. Questions persist, however, about how individual structural subunits are assembled into a functional holoenzyme. Here, we focus on what is known and what remains to be learned about the accessory proteins that facilitate Cu A site maturation. COX is a multi-subunit enzyme of dual genetic originCOX is a member of the A1 subgroup of a diverse superfamily of hemecopper oxidases. Embedded in the inner mitochondrial membrane, it is a multimeric protein complex comprised of structural subunits that are encoded by two distinct genomes. The three largest of these, COX1-3, are mitochondrially-encoded and form the catalytic core of the enzyme. COX1 contains the two heme (a, a 3 ) moieties and a mononuclear Cu B center, all of which are buried within the lipid bilayer in the fully assembled holoenzyme. COX2 harbors a mixed valence, binuclear Cu A site within a cupredoxin fold that is localized to the intermembrane space (IMS) and is solvent exposed. The Cu A site accepts electrons from cytochrome c, and subsequent electron transfer steps to the heme a and then the heme a 3 -Cu B metal centers of COX1 ultimately allow COX to convert molecular oxygen to water. Four protons are pumped across the membrane during each catalytic cycle, and contribute to the electrochemical gradient that is required for aerobic ATP production. The catalytic core is surrounded by a variable number of nuclear-encoded structural subunits (8 in yeast, 11 in humans), which function collectively to stabilize the holoenzyme, provide sites for the allosteric modulation of its catalytic activity, and facilitate its organization into higher order structures termed supercomplexes or respirasomes (reviewed in (1,2)). High resolution structures of mammalian COX (3) and of mammalian respirasomes that contain COX (8,(4) have been invaluable to advancing our understanding of how inter-subunit interactions impinge upon enzyme activity and dimerization, and the integration of COX into higher order structures.http://www.jbc.org/cgi

show abstract

Knockdown of Human Oxa1l Impairs the Biogenesis of F1Fo-ATP Synthase and NADH:Ubiquinone Oxidoreductase

Cited by 80 publications

References 43 publications

Independent gene duplications of the YidC/Oxa/Alb3 family enabled a specialized cotranslational function

Independent gene duplications of the YidC/Oxa/Alb3 family enabled a specialized cotranslational function

Novel SLC7A7 large rearrangements in lysinuric protein intolerance patients involving the same AluY repeat

Building the CuA site of cytochrome c oxidase: A complicated, redox-dependent process driven by a surprisingly large complement of accessory proteins

Contact Info

Product

Resources

About